The long range purpose of this project is to investigate the role of type C retroviruses as an etiologic agent and a vector of genetic information for neoplasia and the use of viral and cellular mutants to analyze the mechanism of regulation of gene expression associated with cell differentiation and oncogenesis. The expression of cellular oncogenes are also investigated. The topics of current interest are: 1) in vitro transmission of the human T cell leukemia virus (HTLV) to nonlymphoid cell lines; 2) HTLV-antibody and virus isolation studies on drug addicts and homosexual patients in D.C. area; 3) oncogene rearrangement, amplification, and expression in human hepatocellular carcinomas, teratocarcinomas, choriocarcinomas, murine reticulum cell neoplasms, and trophoblastic tumors; 4) regulation of retroviral replication in murine trophoblastic tumor cells. Preliminary results indicate that HTLV (type I) can infect at least some nonlymphoid cells of nonhuman origin, and manifest viral activities through morphological alteration of the cell clones isolated after infection. The un usually high rate of HTLV-I antibody positive serum among the drug addicts in the D.C. area may indicate that exposure to the virus of HTLV-family is not infrequent in this population. Rearrangement and/or amplification of c-myc or c-ras have not been detected in cell culture lines derived from human hepatoma, teratocarcinoma, and choriocarcinoma. Other oncogenes are being tested. Although murine trophoblastic tumor cells are not permissive for type C retrovirus replication, the virus can be activated by treating the infected cells with iododeoxyuridine or azacytidine. Studies on the regulation of integrated viral genome and oncogene of these cells are in progress.